We propose to carry out research investigations in the following areas: 1. Chemical and biological characterization of novel actinomycins containing cis- or trans-4-chloroproline. Continue studies to obtain crystalline actinomycins containing cis-4-chloroproline. Prepare by directed biosynthesis actinomycins and trans-4-methylproline replacing proline in the antibiotic peptide. The cis and trans-4-methylproline actinomycins will then be further characterized biologically and chemically. 2. Continue studies on the mechanism of racemization of L-amino acids (e.g., L-valine to their D-enantiomers. 3. Investigate the nature of the novel actinomycins (Z components, Micromonospora-produced compounds) and characterize the unusual amino acids (D-amino acids, N-Methylamino acids, imino acids present in these actinomycins. 4. Study the biosynthesis of actinomycin and the constituent amino acid residues employing cell-free systems and intact organisms. 5. Continue genetic and biochemical studies to establish the role of tryptophan and its metabolism in the biosynthesis of the actinomycin chromophore. BIBLIOGRAPHIC REFERENCES: Lee, B.K., R.G. Condon, G.H. Wagman and E. Katz. Micromonospora-produced gentamycin components. Antimicrobial Agents and Chemotherapy 9, 151-159, 1976. Yajima, T., K.T. Mason and E. Katz. Biogenetic origin of the D-isoleucine and N-methyl-L-alloisoleucine residues in the actinomycins. Antimicrobial Agents and Chemotherapy 9, 224-232, 1976.